This invention relates to a novel reaction apparatus for enabling a chemical reaction to be carried out simply and efficiently, and more particularly to an apparatus most suitable for automatically processing various steps of a chemical reaction. For example, this apparatus is not only usable in a wide range of chemical industries including biochemistry but also adaptable for efficiently processing various tests in biochemical and microbiochemical studies and in clinical diagnosis.
Chemical reactions are classified under a large number of types. Generally in any chemical reaction, the conditions such as temperature, pressure, time, light, and stirring under which the reaction is carried out have very large effects upon the results of the reaction. Among these factors, stirring has an conspicuous effect on the chemical reaction involved. Chemical reaction apparatuses are provided, therefore, with various stirring means adapted specifically to suit their purposes. For a large chemical reaction apparatus, a stirring device normally in the form of a propeller is set inside a tank. Then, optimal reaction conditions are established theoretically and empirically by the selection of the shape of the propeller, the variation of the rotation speed of the propeller, etc. The incorporation of such a stirring device as a propeller, however, becomes increasingly difficult as the reaction container diminishes in size. In the culture of a microorganism, the operation of stirring is simplified by collectively shaking the reaction containers.
The conventional stirring method described in the preceding paragraph, however, has a disadvantage such that the uniformity of stirring decreases in proportion as the reaction containers diminish in size.
In recent years, the practice of diagnosing various diseases by using various chemical reactions, particularly immunochemical reactions, has been finding growing acceptance. The specimen for this diagnosis is mainly the blood of a given patient. Since this amount of blood is limited and must be used for various tests, the amount of blood available for each test would become quite small. Consequently, the reaction containers used for individual test items are liable to come in smaller sizes. Since no effective means of stirring had been proposed for use in such small chemical reaction containers, it was inevitably necessary to let the reaction containers stand without any stirring until the reactions initiated therein proceeded amply. Thus there had been a disadvantage such that the total reaction time took several hours to several days.
Despite this disadvantage, immunochemical reaction using a radioisotope or an enzyme is frequently resorted to in the diagnosis of cancer and many other diseases. This is because this reaction decisively excels over other methods of diagnosis in both sensitivity and reliability. The presence or absence of a disease and the condition of the disease are determined by accurate measurement of the contents of substances in the blood which serve as criteria for diagnosis. Thus, increasing significance has come to be placed on the accuracy and the reliability of the measurement in recent years.
At present for such diagnosis the use of immobilized antibodies is widely accepted. As the solid phase for immobilizing antibody, finely divided particles or beads made of plastic or glass are used. At times, the lower part of the inner surface of the reaction container may be utilized as the solid phase. Generally in a chemical reaction, the components which take part in the reaction are dissolved in a homogeneous solution and are allowed to move freely therein. The chemical reaction is accelerated when the solution is stirred or otherwise agitated so that the components therein will be given a better chance of mutual collision. If any of the components taking part in the chemical reaction is immobilized onto a solid surface, the mutual collision of the components is greatly restrained and consequently the speed of the chemical reaction notably decreases. In such a case, stirring is used as a means of promoting the progress of the reaction. A solution, however, has not yet been found to overcome the aforementioned disadvantages which occur particularly when using a multiplicity of reaction containers each of a small volume.
The instant inventors and his colleagues continued the search for a solution to the problems encountered by the conventional technique as described in the preceding paragraph. They have consequently found that particularly in the case of small reaction containers where a stirring apparatus such as a propeller cannot be inserted, the inclined rotation of the containers themselves brings about faster reaction and highly accurate results.
The present invention has been accomplished on the basis of this knowledge of the inventors. The instant inventor and his colleagues have already devised several inclined rotation apparatuses. One of the apparatuses (type A) comprises a multiplicity ("n" in number) of rollers possessed of a fixed diameter approximating the diameter of cylindrical reaction containers and juxtaposed in parallel and inclined at a fixed angle, so that the reaction containers (a total of "n-1" in number) placed one each on every two adjacent rollers will be rotated by the rotation of the rollers in one direction at a fixed speed (Japanese patent application Laid-open No. SHO 58(1983)-36631, U.S. Pat. No. 4,482,636). Another of the apparatuses (type B) comprises two parallel chains each provided thereon with a multiplicity of freely rotatable equally spaced rollers such that every two adjacent rollers on one of the two chains will support the reaction containers near the mouth and every two adjacent rollers at the corresponding position on the other chain will support them near the bottom, and as a result, the multiplicity of reaction containers will be held in an inclined position in much the same manner as attained by the rollers of the apparatus of type A described above (Japanese patent application Laid-open No. SHO 58(1983)-36631, U.S. Pat. No. 4,482,636). This apparatus is enabled to impart a desired rotation to the reaction containers by moving in one direction an endless belt adapted to hold down the reaction containers. It is otherwise enabled to effect intermittent delivery of the reaction containers by causing the chains to be driven at fixed intervals of time, whereby each reaction container will stop at the exact position of the preceding container. Yet another of the apparatuses (type C) comprises a multiplicity of cylinders inclined and rotated as inclined at a fixed speed so that the reaction containers inserted one each in the interior of the cylinders will be automatically rotated (Japanese patent application Laid-open No. SHO(1983)-61469, U.S. Pat. No. 4,479,720). Generally, in the performance of a chemical reaction, there must be interposed various steps such as, for example, fractionation, addition of specimen and reagents, washing of reaction containers, and sampling of reaction mixtures for the determination of the degree of progress of reaction. Of the apparatuses described above, that of type A is simple mechanism where the rotation speed can be highly controlled, but it has a disadvantage of hampering incorporation therein of a device permitting further improvement of the mechanism to the semi-automatic or full-automatic level. On the other hand, the apparatus of type B is capable of advancing the reaction containers intermittently at a fixed pitch. Since this apparatus has the reaction containers held down by the belt draped thereon, however, it does not permit ready incorporation therein of a manual or automatic hopper unit capable of supplying reaction containers at the outset of the operation of the apparatus or a unit for release of reaction containers. It also entails the disadvantage that it permits no easy incorporation therein of a mechanism which enables a reaction container located at a desired position to be raised to an upright posture and, therefore, proves inconvenient for the automation of such steps as rinsing the interior of the container and replacement of reaction mixture. The apparatus of type C is convenient for solely manual operation similar to the apparatus of type A. When it is desired to adapt this apparatus so as to permit the aforementioned intermittent advancement of reaction containers similar to type B, the adaptation inevitably entails complication of the mechanism as by the incorporation of a turntable system wherein a plurality of cylindrical holders are equally spaced in a circumference having as its center the central axis perpendicularly intersecting an inclined disk and further wherein each cylindrical holder is adapted to be rotated about its respective axis perpendicularly intersecting the inclined disk, so that the reaction containers in the cylindrical holders will be intermittently advanced by a fixed pitch each time the inclined disk is rotated by one pitch over a fixed time. In the adapted apparatus, when a given step is desired to be carried out with the reaction container held upright, this apparatus necessitates further incorporation of a complicated mechanism because the reaction container cannot be held upright unless it is removed from the cylindrical holder.